The object of this study is to examine the prospect that an important mode of action of the amphetamines and principal amphetamine metabolites, p-hydroxyamphetamine and p-hydroxynorephedrine, is by modulation of the activity and turnover of catecholamine synthesizing enzymes, tyrosine hydroxylase, pteridine reductase, dopa decarboxylase & dopamine-beta-hydroxylase. To accomplish this we first plan to purify the enzymes, characterize the as-yet-to-be-determined properties including the presence of multiple forms of the enzymes, isozymes, produce specific antibodies to each enzyme from three species (cow, rat, man), measure the amounts of enzyme regionally in brain by immunoprecipitation and radio-immunoassay methods and determine the localization immunohistochemically. Then we shall examine the action of amphetamine and metabolites in vitro on the kinetics of the purified enzyme. Finally we shall study the action of acute and chronic administration of amphetamine and amphetamine metabolites on the amounts of enzyme and rates of their synthesis and degradation regionally in brain.